Cytomegalovirus (CMV) is an important cause of death in patients with advanced HIV infection. CMV pneumonia is often found at autopsy, but the diagnosis is rarely established antemortem. Since effective CMV therapy is now available, early and accurate diagnosis of CMV pneumonia may benefit patients. Three populations of HIV-infected patients were studied: volunteers with no pulmonary symptoms and no history of documented or empirically treated CMV disease (Group 1), volunteers with documented CMV retinitis and no pulmonary symptoms (Group 2), and patients with acute pulmonary symptoms (Group 3). Bronchoalveolar lavage (BAL) and transbronchial biopsies were performed. Specimens were assessed for the presence of CMV using microbiologic, cytopathologic, and histopathologic techniques. The CMV pneumonia diagnosis required at least one typical CMV inclusion body in lung tissue and compatible pulmonary abnormalities that did not resolve with treatment for concurrent (if any) processes. Group 1 consisted of 19 volunteers with a mean CD4+ lymphocyte count of 315 cells/mu L. None had histopathologic or cytopathologic evidence of CMV; however, 9 of 19 had CMV-positive BAL cultures-none had detectable CMV antigen. Group 2 consisted of 6 volunteers with a mean CD4+ lymphocyte count of 45 cells/mu L. None had histopathologic or cytopathologic evidence of CMV; however, all had CMV positive BAL cultures, yet no detectable antigen. Group 3 consisted of 46 patients with a mean CD4+ lymphocyte count of 74 cells/mu L. None had histopathologic evidence of CMV; two were positive by cytopathology (CD4+ counts of 0 and 14 cells, respectively). CMV cultures were positive in 33 of 46 patients; CMV antigen was detectable in only 1 patient. We concluded that CMV is frequently cultured from BAL of HIV- infected patients, especially those with CD4+ counts of less than 300 cells/mu L; serious or life-threatening pulmonary dysfunction because of CMV is rarely detectable antemortem; and CMV culture of BAL does not provide diagnostically important information and may not be cost effective. This study was larger than a previously published series and answered a clinical issue using special NIH resources involving the Clinical Center, NIAID, and NCI, and the Food and Drug Administration.